16 results about "Thioredoxin reductase" patented technology

The invention discloses a recombinant bacterium for high-yield production of selenomethionine and a preparation method of the recombinant bacterium, and belongs to the technical field of genetic engineering. According to the invention, selenium-rich region (Enshi) soil and withered grass are taken as materials, a bacillus subtilis strain with high selenomethionine synthesis capability is separated and screened, the bacillus subtilis strain is taken as an original strain, and a recombinant strain of high-expression SeMet synthesis key gene thioredoxin reductase (TrxRB) is constructed by utilizing an expression vector pHT43, so that high-yield SeMet engineering bacteria are obtained. The bacillus subtilis rich in selenomethionine and the recombinant bacteria thereof can be used as feed additives, and can be used for supplementing SeMet and improving the feed conversion rate in the production of livestock and poultry and aquatic animals.

The present application relates to the chemical medicine field, specifically, it relates to a kind of anti-tumor calophyllol derivative, preparation method and application, the calophyllol derivative has good inhibitory effect on thioredoxin reductase activity, and it is found that the molecule inhibits the activity of thioredoxin reductase by inhibiting the selenium cysteine of thioredoxin reductase carbon end, and then kills tumor cell, and then obtain the anti-tumor candidate drug with higher activity and better pharmacokinetic characteristics.

This disclosure provides an E. coli strain, which lacks thioredoxin reductase activity encoded by trxB and thioredoxin 1 activity encoded by trxA, and glutathione reductase activity encoded by gor. Said E. coli strain expresses a mutated AhpC protein having glutathione reductase activity and a cytosolic prokaryotic disulfide isomerase. The E. coli strain has an oxidative cytosol and can be used to efficiently produce proteins having disulfide bonds.

The invention discloses a thioredoxin reductase detection method, which comprises the following steps: preparing a hairpin DNA probe HP solution, an H1 solution and an H2 solution, and carrying out annealing treatment; a pretreatment hairpin type DNA probe HP solution, a pretreatment hairpin type DNA probe H1 solution and a pretreatment hairpin type DNA probe H2 solution are obtained; mixing the three pre-treated hairpin DNA probe solutions, adding an NADPH solution and a sample to be detected, and incubating at 37 DEG C to obtain a solution to be detected; and collecting a fluorescence signal of the to-be-detected solution through a multifunctional microplate reader, and calculating the concentration of thioredoxin reductase through a linear equation: Y = 730.7 X + 2000.2, Y representing the fluorescence signal and X representing the logarithm LogCTrxR of TrxR concentration. According to the method disclosed by the invention, the detection sensitivity of the TrxR is remarkably improved, and the method is applied to imaging of the TrxR; the method has the advantages of good selectivity, high sensitivity, real-time monitoring and the like.

The invention belongs to the technical field of organic arsine targeting compounds, and particularly relates to a novel targeting compound for treating various cancers as well as a preparation method and application of the novel targeting compound. Core innovations include precise synthesis of an arsine precursor and a process for designing a targeting structure for multiple cancer species. A series of high-purity organic arsine compounds are developed through an advanced organic synthesis technology, and screening optimization is carried out in combination with means such as computational simulation, biomacromolecule interaction analysis, cell experiments and animal models. Results show that the compound has the characteristics of efficient tumor inhibition and low toxicity, especially shows strong inhibition on thioredoxin reductase, prolongs the in-vivo circulation time and reduces the administration frequency. The effect in treatment of the triple-negative breast cancer is remarkable, and the good clinical transformation potential is achieved. The invention aims to protect the chemical structure and the preparation method of the compound and the application of the compound in cancer treatment.

The effects of compositions 2-bromo-2-nitro-1,3-propanediol are discussed herein, including an anticancer effect of the compositions. Methods related to treating cancer in a subject comprising administering compositions comprising 2-bromo-2-nitro-1,3-propanediol and methods related to inhibiting the activity of thioredoxin reductase are also provided. Dosage ranges are disclosed along with compatible treatment regimens.

An enzyme for reducing cystine to cysteine is a fusion protein that includes the protein activities of thioredoxin (protein i) having KEGG database number EC 1.8.4.8 or EC 1.8.4.10 and thioredoxin reductase (protein ii) having KEGG database number EC 1.8.1.9. The thioredoxin (protein i) is the protein activity of thioredoxin 1 from E. coli and the thioredoxin reductase (protein ii) is the protein activity of the thioredoxin reductase from E. coli. The activity of the fusion protein is at least 100% of the activity of a mixture of the same but unfused individual proteins i and ii. The fusion protein has the enzyme activity to reduce cystine to cysteine. The coding sequences (cds) responsible for the activity of protein i and ii has been fused.

The invention relates to a preparation method and application of a coupled drug molecule for synergistic anti-tumor treatment, and belongs to the technical field of medical chemistry and biological medicine. The invention designs and synthesizes a combined prodrug molecule (pAs-DTC) which is formed by connecting an arsenic inhibitor of targeted thioredoxin reductase (TrxR) with dithiocarbamate (DTC) through a pathological switch disulfide bond. The prodrug can be selectively broken under the action of reducing species in tumor cells, the two active components are released, and the aim of synergistically killing the tumor cells is achieved through the combination of targeted inhibition of TrxR activity by the arsenic inhibitor and chelating of DTC with Cu. The invention provides a novel anticancer combined treatment strategy, provides a theoretical basis and a practical basis for developing high-efficiency and low-toxicity antitumor drug combinations, and has a very good clinical application prospect.

The invention discloses a chloroacetamide thioredoxin reductase inhibitor and application of the chloroacetamide thioredoxin reductase inhibitor in preparation of antitumor drugs. The structural formula of the chloroacetamide thioredoxin reductase inhibitor is # imgabs0 #. The chloroacetamide thioredoxin reductase inhibitor disclosed by the invention has a very good inhibition effect on proliferation of various cancer cell strains in vitro and can inhibit pure thioredoxin reductase and intracellular thioredoxin reductase, and the inhibition activity and selectivity of the inhibitor are superior to those of positive medicaments, namely Jinnofen, TRI-1 and TRI-2.

The invention discloses thioredoxin reductase BrgTrxR, the amino acid sequence of the thioredoxin reductase BrgTrxR is shown as SEQ ID NO: 1, the gene is obtained from a Brevibacillus gelatini LD5 strain, the protease is subjected to heterologous expression through a genetic engineering means, the protease is purified through a nickel column and is mixed with keratinase BrgM4 to degrade chicken feather, experimental data shows that the activity of the reductase reaches 15.81 U / mg after the reductase is separated and purified, and the activity of the reductase reaches 15.81 U / mg after the reductase is mixed with keratinase BrgM4. In a mixed degradation system with the temperature of 40-80 DEG C and the pH value of 6.5-7.5, the thioredoxin reductase BrgTrxR can improve the hydrolytic activity of the keratinase BrgM4, after the chicken feather is degraded for 48 h through the synergistic effect of the two enzymes, the concentration of soluble protein reaches 14.45 mg / mL, and the thioredoxin reductase is beneficial to cooperating with the keratinase to improve the keratin degradation efficiency.

The invention relates to the technical field of preparation of anti-cancer drugs, in particular to a Schiff base gold (III) compound and a preparation method and application thereof.The series of symmetric or asymmetric Schiff base gold (III) compounds are synthesized on the basis of the bioisostere principle in combination with a Schiff base ligand, the cyclohexanediamine structure and the NNOO coordination mode of oxaliplatin are reserved, platinum (II) is replaced with gold (III), and the Schiff base gold (III) compound is synthesized. Meanwhile, the invention relates to application of the Schiff base gold (III) compound in preparation of anti-hepatoma drugs, the defects that oxaliplatin is strong in side effect and the like are overcome, in-vivo and in-vitro experiment results of the Schiff base gold (III) compound provided by the invention show that the compounds Au3 and Au7 are remarkable in anti-hepatoma activity and can target thioredoxin reductase (TrxR) and mitochondrial DNA (mtDNA) at the same time, and the Schiff base gold (III) compound can be used for preparing anti-hepatoma drugs. The further mechanism research shows that the compound can promote the generation of reactive oxygen species (ROS) to cause endoplasmic reticulum stress (ERS) and mitochondrial injury and finally induce pyroptosis and immunogenic cell death, and has great application potential.

The present application belongs to the technical field of chemistry, pharmacy, medicine and other multi-disciplinary, more specifically, a kind of hydroxyalkyl starch-photosensitizer coupled amphiphilic macromolecular compound, nano drug delivery system and its preparation method and application are disclosed.The present application uses hydrophobic porphyrin heterocyclic macrocyclic organic compound photosensitizer as the hydrophobic end, coupled with hydroxyalkyl starch, and assembled into nanoparticles with hydroxyalkyl starch-platinum (IV) conjugate.The experiment found that the amphiphilic macromolecular compound can improve the water solubility of photosensitizer, and also can maintain the photodynamic characteristics of photosensitizer, give its targeting tumor characteristics, improve the bioavailability of photosensitizer, and the added hydroxyalkyl starch-platinum (IV) conjugate can release cisplatin in vivo, inhibit the activity of thioredoxin reductase, destroy the tumor redox balance, promote the effect of photodynamic therapy, realize the targeted combination therapy of antitumor drugs.

This invention belongs to the field of medicinal chemistry and pharmaceutical technology, and discloses a pyrano[2,3-a]phenazine derivative, its preparation method, and its application in the preparation of anti-glioma drugs. The structural formula of the pyrano[2,3-a]phenazine derivative is as follows: R1 is H, halogen, or -N(C2H5)2; R2 is H or halogen; R3 is H, halogen, or -CH3; R4 is H or halogen; R5 is H, halogen, or -OCH3; R6 is H, halogen, -CH3, -C2H5, or -OCH3; R7 is H or -OCH3; X is -CN or -COOC2H5. This invention also discloses the preparation method of this pyrano[2,3-a]phenazine derivative and its application in the preparation of anti-glioma drugs. This type of compound has a strong inhibitory effect on thioredoxin reductase (TrxR) and significant inhibitory activity against human glioma cells (U87), showing great application potential in the preparation of anti-glioma drugs.

The invention discloses a preparation method and application of prodrugs CPT-40 and CPT-38 based on camptothecin, and belongs to the technical field of medicines. The invention aims to solve the technical problems of poor water solubility, low in-vivo stability and large toxic and side effects of the existing camptothecin drugs. The key point of the technical scheme of the invention is to provide a CPT-40 compound as shown in a formula (I) and a CPT-38 compound as shown in a formula (II), a preparation method of the CPT-40 compound and the CPT-38 compound, and application of the CPT-40 compound and the CPT-38 compound in preparation of antitumor drugs. The prodrug can be specifically activated by thioredoxin reductase highly expressed in tumor tissues to release active camptothecin so as to kill tumor cells. The compound is mainly used for preparing drugs for targeted therapy of tumors, and has the advantages of high selectivity, good plasma stability and high oral bioavailability.

This disclosure provides an E. coli strain, which lacks thioredoxin reductase activity encoded by trxB and thioredoxin 1 activity encoded by trxA, and glutathione reductase activity encoded by gor. Said E. coli strain expresses a mutated AhpC protein having glutathione reductase activity and a cytosolic prokaryotic disulfide isomerase. The E. coli strain has an oxidative cytosol and can be used to efficiently produce proteins having disulfide bonds.

Seminaphthofluorophore-selenium probes are disclosed. The probes include a seminaphthofluorophore scaffold substituted with at least one diselenide moiety having a formula —Y—C(Q)O—(CH2)m—Se—Se—(CH2)n—ORf, where Rf is hydrogen or C1-C3 alkyl, Q is O or S, Y is O or N(Rg) where Rg is H or alkyl, and m and n independently are integers. The probes may be used to detect presence of a thioredoxin reductase.